PMID- 28656223
OWN - NLM
STAT- MEDLINE
DCOM- 20180510
LR  - 20211204
IS  - 1791-3004 (Electronic)
IS  - 1791-2997 (Print)
IS  - 1791-2997 (Linking)
VI  - 16
IP  - 2
DP  - 2017 Aug
TI  - Rapamycin inhibits CaCl2-induced thoracic aortic aneurysm formation in rats 
      through mTOR-mediated suppression of proinflammatory mediators.
PG  - 1911-1919
LID - 10.3892/mmr.2017.6844 [doi]
AB  - The aim of the present study was to investigate the effect of the mammalian 
      target of rapamycin (mTOR) signaling pathway on thoracic aortic aneurysm (TAA) 
      development. The study used a calcium chloride (CaCl2)‑induced rat TAA model to 
      explore the potential role of mTOR signaling pathway in the disease development. 
      Adult male Sprague‑Dawley rats underwent the periarterial exposure of thoracic 
      aorta to either 0.5 M CaCl2 or normal saline, and a subgroup of CaCl2‑treated 
      rats received rapamycin 1 day prior to surgery. Without pre‑administering 
      rapamycin, significantly enhanced phosphorylation of mTOR and expression of 
      proinflammatory cytokines [i.e., tumor necrosis factor alpha (TNF‑alpha), interleukin 6 
      (IL‑6), and interleukin (IL)‑1beta] were observed in the CaCl2‑treated aortic 
      segments 2 days post‑treatment compared with the NaCl‑treated segments. At 
      2 weeks post‑treatment, hematoxylin and eosin and Verhoeff‑Van Gieson staining 
      revealed aneurysmal alteration and disappearance of normal wavy elastic 
      structures in the aortic segments exposed to CaCl2. In contrast, the 
      CaCl2‑induced TAA formation was inhibited by pre‑administering rapamycin to 
      CaCl2‑treated rats, which demonstrated attenuated mTOR phosphorylation and 
      downregulation of the proinflammatory mediators (i.e., TNF‑alpha, IL‑6, IL‑1beta, matrix 
      metallopeptidases 2 and 9) to the control level. Further in vitro cell culture 
      experiments using aortic smooth muscle cell (SMC) suggested that the inhibition 
      of the mTOR signaling pathway by rapamycin could promote the differentiation of 
      SMCs, as reflected by the reduced expression of S100A4 and osteopontin. The 
      present study indicated that the early enhanced mTOR signaling pathway in the TAA 
      development and mTOR inhibitor rapamycin may inhibit CaCl2‑induced TAA formation.
FAU - Cao, Jiumei
AU  - Cao J
AD  - Department of Geratology, Ruijin Hospital, Shanghai Jiaotong University School of 
      Medicine, Shanghai 200025, P.R. China.
FAU - Wu, Qihong
AU  - Wu Q
AD  - Department of Cardiology, Ruijin Hospital, Shanghai Jiaotong University School of 
      Medicine, Shanghai 200025, P.R. China.
FAU - Geng, Liang
AU  - Geng L
AD  - Department of Cardiology, Ruijin Hospital, Shanghai Jiaotong University School of 
      Medicine, Shanghai 200025, P.R. China.
FAU - Chen, Xiaonan
AU  - Chen X
AD  - Department of Geratology, Ruijin Hospital, Shanghai Jiaotong University School of 
      Medicine, Shanghai 200025, P.R. China.
FAU - Shen, Weifeng
AU  - Shen W
AD  - Department of Cardiology, Ruijin Hospital, Shanghai Jiaotong University School of 
      Medicine, Shanghai 200025, P.R. China.
FAU - Wu, Fang
AU  - Wu F
AD  - Department of Geratology, Ruijin Hospital, Shanghai Jiaotong University School of 
      Medicine, Shanghai 200025, P.R. China.
FAU - Chen, Ying
AU  - Chen Y
AD  - Department of Cardiology, Ruijin Hospital, Shanghai Jiaotong University School of 
      Medicine, Shanghai 200025, P.R. China.
LA  - eng
PT  - Journal Article
DEP - 20170622
PL  - Greece
TA  - Mol Med Rep
JT  - Molecular medicine reports
JID - 101475259
RN  - 0 (Biomarkers)
RN  - 0 (Inflammation Mediators)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - EC 3.4.24.24 (Matrix Metalloproteinase 2)
RN  - EC 3.4.24.35 (Matrix Metalloproteinase 9)
RN  - M4I0D6VV5M (Calcium Chloride)
RN  - W36ZG6FT64 (Sirolimus)
SB  - IM
MH  - Animals
MH  - Aortic Aneurysm, Thoracic/*chemically induced/*drug therapy
MH  - Biomarkers/metabolism
MH  - Calcium Chloride
MH  - Cell Differentiation/drug effects
MH  - Cells, Cultured
MH  - Inflammation Mediators/*metabolism
MH  - Male
MH  - Matrix Metalloproteinase 2/metabolism
MH  - Matrix Metalloproteinase 9/metabolism
MH  - Myocytes, Smooth Muscle/metabolism
MH  - Rats, Sprague-Dawley
MH  - Signal Transduction/drug effects
MH  - Sirolimus/pharmacology/*therapeutic use
MH  - TOR Serine-Threonine Kinases/*metabolism
PMC - PMC5561979
EDAT- 2017/06/29 06:00
MHDA- 2018/05/11 06:00
PMCR- 2017/06/22
CRDT- 2017/06/29 06:00
PHST- 2016/05/31 00:00 [received]
PHST- 2017/04/05 00:00 [accepted]
PHST- 2017/06/29 06:00 [pubmed]
PHST- 2018/05/11 06:00 [medline]
PHST- 2017/06/29 06:00 [entrez]
PHST- 2017/06/22 00:00 [pmc-release]
AID - mmr-16-02-1911 [pii]
AID - 10.3892/mmr.2017.6844 [doi]
PST - ppublish
SO  - Mol Med Rep. 2017 Aug;16(2):1911-1919. doi: 10.3892/mmr.2017.6844. Epub 2017 Jun 
      22.